Respiratory ciliopathies including non-CF bronchiectasis

Gene: RAG2

Green List (high evidence)

RAG2 (recombination activating 2)
EnsemblGeneIds (GRCh38): ENSG00000175097
EnsemblGeneIds (GRCh37): ENSG00000175097
OMIM: 179616, Gene2Phenotype
RAG2 is in 7 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on publications: added further publications to support gene-disease association and rating of this gene to Green
Created: 22 Jan 2019, 10:28 a.m.
Update from From GMS Respiratory Specialist Test Group member Ian Berry. Suggested phenotype from Sinisa Savic : Combined immunodeficiency (CID), and combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A) are both associated with early onset and progressive lung disease.
Created: 22 Jan 2019, 10:16 a.m.
From GMS Respiratory Specialist Test Group webex call 18th Jan 2019: agreed there is enough evidence to rate this gene Green. Ian Berry to check with Sinisa Savic and Daniel Peckham re. phenotype
Created: 21 Jan 2019, 5:31 p.m.
Comment on list classification: New gene added by external reviewer. To be reviewed in GMS Respiratory specialist test group 18th Jan 2018. Confirm phenotype, MOI and rating
Created: 17 Jan 2019, 11:20 a.m.
Comment on publications: Added publication suggested by external reviewer to support support gene-disease association
Created: 17 Jan 2019, 11:20 a.m.

Ian Berry (Leeds Genetics Laboratory)

Green List (high evidence)

Results in varying severity phenotypes of immunodeficiency, including hypomorphic mutations resulting in CVID. Two patients have been seen in our bronchiectasis clinic with "leaky" RAG mutations and mild symptoms including bronchiectasis, with limited additional immunological findings. Bronchiectasis (with immunological phenotype) is a common feature of RAG-CVID, see e.g. PMID 24996264. Expert review by Dr Sinisa Savic (Clinical Immunologist) and Dr Daniel Peckham (Respiratory Physician), bronchiectasis expert team from Leeds.
Sources: Expert Review
Created: 11 Jan 2019, 4:46 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Combined immunodeficiency (CID)
  • Combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A)
  • early onset and progressive lung disease
OMIM
179616
Clinvar variants
Variants in RAG2
Penetrance
None
Publications
Panels with this gene

History Filter Activity

27 Sep 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: RAG2 were changed from Combined immunodeficiency (CID); Combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A) to Combined immunodeficiency (CID); Combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A); early onset and progressive lung disease

22 Jan 2019, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: RAG2 were set to 24996264

22 Jan 2019, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: RAG2 were changed from to Combined immunodeficiency (CID); Combined immunodeficiency with granuloma and/or autoimmunity (CID-G/A)

17 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: rag2 has been classified as Green List (High Evidence).

17 Jan 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: rag2 has been classified as Amber List (Moderate Evidence).

17 Jan 2019, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: rag2 has been classified as Green List (High Evidence).

17 Jan 2019, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: RAG2 were set to

17 Jan 2019, Gel status: 1

Added New Source, Status Update

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to RAG2. Rating Changed from No List (delete) to Red List (low evidence)

11 Jan 2019, Gel status: 0

Created, Added New Source, Set mode of inheritance

Ian Berry (Leeds Genetics Laboratory)

gene: RAG2 was added gene: RAG2 was added to Respiratory ciliopathies including non-CF bronchiectasis. Sources: Expert Review Mode of inheritance for gene: RAG2 was set to BIALLELIC, autosomal or pseudoautosomal Review for gene: RAG2 was set to GREEN gene: RAG2 was marked as current diagnostic